Pathological gambling is a highly underrated, yet extremely serious public health problem with enormously detrimental effects on individuals and families, and with an estimated yearly cost to society of over 5 billion dollars due to lost jobs, debt, bankruptcy, and incarcerations. Despite growing public awareness of the prevalence and damaging consequences of PG, there is presently no established psychosocial treatment for PG and no FDA approved medications. Through extensive pilot work and an NIMH-funded randomized trial (R21 MH064568) we have developed a treatment termed Cognitive-Motivational Behavior Therapy (CMBT) that has shown excellent retention and treatment efficacy. CMBT helps pathological gamblers resolve their motivational ambivalence and increases their readiness to change. Once patients are committed to change, the CMBT therapist then systematically corrects their specific cognitive biases, teaches them coping and resistance skills, and encourages lifestyle changes to innoculate them against relapse. Using the 'Collaborative R01s for Clinical Studies of Mental Disorders'mechanism, we now propose to conduct a study to identify mediators and moderators of this innovative treatment and to test its efficacy in a large randomized controlled trial with 200 pathological gamblers. We will randomize gamblers to CMBT or Cognitive-Behavioral Therapy (CBT) as a comparison condition and assess them before, during, and after treatment as well as at 3, 6, and 12-month follow-up. We hypothesize that the effect of CMBT will be mediated by readiness to change, cognitive distortions, coping skills, and therapeutic alliance, whereas CBT will be mediated only by the last three, since it does not specifically target motivation. Hypothesized moderators include psychiatric comorbidity, baseline levels of gambling severity and of motivation to change, impulsivity and family history of PG. Specifically, we hypothesize that although CMBT will be superior on average to CBT in improving treatment retention and decreasing gambling behavior, those differences will be even larger in the presence of psychiatric comorbidity or family history of PG, higher baseline levels of impulsivity or gambling severity, or in individuals with lower motivation to change. We are confident that the findings from this study will significantly improve our understanding of PG and inform future research on the treatment of this very recalcitrant and difficult psychological disorder. PUBLIC HEALTH RELEVANCE: Pathological gambling (PG) is a serious public health problem with enormously detrimental effects on individuals and families, yet there is a paucity on treatments of proven efficacy for this disorder. After developing Cognitive-Motivational Behavior Therapy (CMBT) and testing it in a small NIMH-funded randomized trial (R21 MH064568), we propose to conduct a rigorous large-scale efficacy trial comparing CMBT versus Cognitive-Behavioral Therapy to identify treatment mediators and moderators of both treatment approaches. The findings from this study will significantly improve our understanding of PG and inform future research on this disorder.